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Dose Confirmation and Dose Expansion Phase 1 Study of IO-108 and IO-108 + Anti-PD-1 in Solid Tumors

Phase 1
Completed
Conditions
Advanced Solid Tumor
Interventions
Biological: IO-108
Biological: IO-108 + pembrolizumab
Biological: IO-108 + tislelizumab
Registration Number
NCT05508100
Lead Sponsor
Immune-Onc Therapeutics
Brief Summary

This is a Phase 1 study to evaluate the safety, tolerability, PK, and preliminary efficacy of IO-108 monotherapy and in combination with anti-PD-1 monoclonal antibody pembrolizumab or tislelizumab in adult patients with advanced solid tumors. The study will be conducted in 3 parts, including Part A IO-108 monotherapy dose confirmation; Part B IO-108 + anti-PD-1 dose confirmation, and Part C dose expansion.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
38
Inclusion Criteria
  1. Age ≥18, and < 75.

  2. Part A and Part B Cohort 1: Patients must have histologically or cytologically confirmed advanced or metastatic solid tumor and have failed, or have been intolerant for standard systemic therapy, or for whom no treatment known to confer clinical benefit exists.

    Part B Cohort 2 and Part C: Patient with advanced or metastatic solid tumor who meet the specific criteria.

  3. Patients have at least 1 measurable disease per RECIST v1.1 as assessed by local clinical site.

  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

  5. Patients must have adequate hematologic function, hepatic function and renal function.

Exclusion Criteria
  1. Patients who previously received a monoclonal antibody therapy targeting LILRB2/ILT4 (including IO-108).
  2. Patients who received chemotherapy, radiotherapy, biologic therapy, targeted therapy, immunotherapy, or other investigational anti-cancer therapy < 4 weeks prior to their first day of study drug administration.
  3. Requires systemic corticosteroids at a dose of >10 mg daily of prednisone or the dose equivalent to other systemic corticosteroid, or other immunosuppressive agents ≤ 14 days prior to the first dose.
  4. History of radiation pneumonitis, non-infectious pneumonitis or interstitial lung disease expect for radioactive pulmonary fibrosis not requiring corticosteroid treatment.
  5. Symptomatic central nervous system (CNS) metastases. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part A: IO-108 monotherapy dose confirmationIO-108Patients with advanced or metastatic solid tumors will be enrolled and treated with IO-108, intravenously, every 21 days.
Part B: IO-108 + anti-PD-1 dose confirmation.IO-108 + tislelizumabPatients will receive IO-108 in combination with with a fixed dose of pembrolizumab, intravenously, every 21 days; Patients will receive IO-108 in combination with with a fixed dose of tislelizumab, intravenously, every 21 days.
Part C: Dose expansionIO-108 + pembrolizumabPatients with advanced or metastatic solid tumors who meet the specific criteria will be enrolled into one of the cohorts.
Part B: IO-108 + anti-PD-1 dose confirmation.IO-108 + pembrolizumabPatients will receive IO-108 in combination with with a fixed dose of pembrolizumab, intravenously, every 21 days; Patients will receive IO-108 in combination with with a fixed dose of tislelizumab, intravenously, every 21 days.
Part C: Dose expansionIO-108 + tislelizumabPatients with advanced or metastatic solid tumors who meet the specific criteria will be enrolled into one of the cohorts.
Primary Outcome Measures
NameTimeMethod
Preliminary anti-tumor activity of IO-108 in combination with pembrolizumab or tislelizumabthrough study completion, an average of 2 years

ORR is defined as the percentage of patients who have a complete response (CR) or a partial response (PR) per RECIST v1.1

Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) in patients treated with IO-108through study completion, an average of 2 years

AE severity graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0

Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) in patients treated with IO-108 in combination with pembrolizumab or tislelizumabthrough study completion, an average of 2 years

AE severity graded by NCI CTCAE, Version 5.0

Secondary Outcome Measures
NameTimeMethod
Preliminary anti-tumor activitythrough study completion, an average of 2 years

Progression-free Survival, defined as the time interval from the first dose date to the occurrence of disease progression or death of any cause

Steady state concentration of IO-108through study completion, an average of 2 years

Characterize steady state concentration of IO-108 by successive sampling of blood at pre-specified time points

Anti-drug antibodies (ADA) of IO-108through study completion, an average of 2 years

Determine the incidence and titer of ADAs against IO-108

Maximum plasma concentration (Cmax) of IO-108through study completion, an average of 2 years

Characterize the Cmax of IO-108 by successive sampling of blood at pre-specified time points

Trial Locations

Locations (14)

Harbin Cancer Hospital

🇨🇳

Harbin, Heilongjiang, China

The First Affiliated Hospital of Nanchang University

🇨🇳

Nanchang, Jiangxi, China

Liaoning Cancer Hospital

🇨🇳

Shenyang, Liaoning, China

Shandong Cancer Hospital

🇨🇳

Jinan, Shandong, China

1st Affiliated Hospital of Xi'an Jiaotong University

🇨🇳

Xian, Shanxi, China

4th Hospitla of Hebei Medical University

🇨🇳

Shijia Zhuang, Hebei, China

Tongji Hospital

🇨🇳

Wuhan, Hubei, China

1st affiliated Hospital of Hainan Medical University

🇨🇳

Haikou, Hainan, China

Lin Yi Cancer Hospital

🇨🇳

Linyi, Shandong, China

The First Affiliated Hospital of Fujian Medical University

🇨🇳

Fujian, Fuzhou, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

Shanghai Dong Fang Hospital

🇨🇳

Shanghai, Shanghai, China

Sir RUN RUN SHAW HOSPITAL

🇨🇳

Hangzhou, Zhejiang, China

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